The goal of this project is to fill gaps in our understanding of the antecedents of heart disease in South Asians, specifically focusing on coronary artery calcified plaque. We have established a prospective cohort of South Asians called the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study which is closely tied to the Multi-Ethnic Study of Atherosclerosis (MESA) for efficient cross-ethnic comparisons. We have found that South Asians have significantly higher prevalence of several traditional cardiovascular risk factors, a unique distribution of ectopic body fat deposition, and a high coronary artery calcium burden. We propose to leverage the MASALA cohort baseline data by measuring plaque progression and adding novel measures of coronary plaque to investigate the epidemiology, etiology and natural history of atherosclerotic cardiovascular disease (ASCVD) in South Asians. In this renewal of the MASALA study grant, we propose to determine the progression of coronary plaque by repeating a cardiac computed tomography scan, measure advanced coronary plaque characteristics (calcium density and plaque distribution) from existing baseline scans, and identify the key predictors of ASCVD events among approximately 875 South Asians. Our aims are to 1) investigate the rate of CAC progression among South Asians after 4 years of follow-up, and compare annualized progression rates to the MESA race/ethnic groups; 2) determine the prevalence and correlates of advanced coronary plaque characteristics among South Asians and compare the prevalence and correlates with the four MESA race/ethnic groups; and 3) determine whether CAC and coronary plaque characteristics are associated with incident myocardial infarction and ASCVD events among South Asians. Studying this high risk ethnic cohort could provide novel insights into the pathogenesis of atherosclerotic disease that cannot be observed in studies focusing on other race/ethnic groups.